By NIH3T3 transfection assay in conjunction with in vitro transient neomycin selection, activated c-H-ras-1 oncogenes were detected in two squamous cell carcinoma cell lines, ZA and HOC-313, newly established from human oral cancer patients. ZA had a point mutational activation at the 13th codon, this activation of c-H-ras-1 being novel in human cancer cells, while HOC-313 appeared to have an activation at the 12th codon. In ZA, 16- to 32-fold amplification of the EGF receptor gene, c-erbB-1 and a few-fold amplification of c-myc were detected. The significance of these findings is discussed in relation to multistep carcinogenesis in human cells.